The present applicants were co-inventors of previous patent applications relating to novel spiro-quinuclidine compounds, in which oxathiolane rings were connected in spiro manner with quinuclidine rings, see e.g. European Patent Application No. 0205247 A2, published Dec. 17, 1986, and U.S. Pat. Nos. 4,855,290 (issued Aug. 8, 1989), 4,981,858, (issued Jan. 1, 1991), 4,900,830 (issued Feb. 13, 1990) and 4,876,620 (issued Oct. 24, 1989), the contents of all of which are incorporated herein by reference. These novel compounds were found to possess central nervous system activity. The biological activity of the compound 2-methylspiro(1,3-oxathiolane-5',3)quinuclidine, which exists as geometrical cis- and trans-isomers depending upon whether the 2-methyl group is located on the same side of the oxathiolane ring as the quinuclidine ring nitrogen atom (cis) or on the other side of the quinuclidine ring nitrogen atom (trans), was in particular extensively investigated, and it was found on the basis of pre-clinical tests that the cis- compound might be especially promising for the control of senile dementia of Alzheimer's type (SDAT). It is also of interest that each of the cis- and trans-isomers may be optically resolved, and the biological activity of the optical isomers was also investigated in a number of cases.
It is a principal object of the invention to provide novel spiro-1,3-oxazoline/bridged-ring compounds, which are distinctive from the aforementioned spiro-oxathiolane/quinuclidine compounds. Further objects of the invention, and especially those which relate to the provision of useful pharmaceutical compositions and methods for the treatment of disease in mammals, will be apparent from the description which follows.